Background and Objectives We have shown that human monocytes but not T or B cells, when stimulated with heat-killed B. burgdorferi, induced at the mRNA level, IL-1 , IL-6 and IL-10 cytokine gene transcripts. We also showed that the monocytic cell line THP-1 responded to heat-killed B. burgdorferi and lipidated OspA (L--OspA) by producing IL-6 and IL-10 in a dose dependent fashion. The objectives of this research were to assess whether CD14 is involved as a receptor for B. burgdorferi lipoproteins. THP-1 cells were incubated with increasing concentrations of monoclonal antibodies (MAbs) that bind to CD14. This was done in order to assess if MAb binding would inhibit the production of IL-6 and IL-10 by the THP-1 cells after exposing them to lipoproteins. LPS was used as a positive control. The MAbs were MY4 and 60bca, which bind to the portion of CD14 which interacts with LPS, and 26ic, which also binds to CD14 but not at the receptor's active site for LPS binding. The stimulants employed were LPS, L-OspA and also Pam3Cys-Ser-Lys4-OH, a derivative that contains only the lipid moiety of such lipoproteins attached to a hexapeptide (Pam3Cys). Results Incubation with increasing concentrations of MAbs 60bca and MY4 resulted in an increased inhibition of the production of IL-10 or IL-6 by the THP-1 cells, when the cells were incubated either with the L-OspA or Pam3Cys, whereas incubation with increasing concentrations of the 26ic antibody resulted in no inhibition of IL-10 or IL-6 production. Production of IL-6 or IL-10 by LPS was equally inhibited by the MY4 and 60bca MAbs but not by the 26ic MAb. These results show that the THP-1 cell line could be used as a model for monocytes that are contained in PBMC of humans and nonhuman primates and, more importantly, that CD14, the receptor for LPS, is probably also the receptor for spirochetal lipoproteins. Future directions To definitively identify and purify the receptor for spirochetal